Response to AP-1/Egr1 puzzler

22 November 2000

Fabio Romerio

I can think of a few possibilities. First: it is known that c-fos transcription is upregulated in response to MEK/ERK triggering through activation of the transcription factor Elk-1, which binds the c-fos enhancer. Does Elk-1 bind also to the Egr promoter/enhancer? Second: STAT1 and STAT3 are regulated by tyrosine phosphorylation, but for full activity they require also phosphorylation in serine (see papers by Doreen Cantrell and also by Andrew Larner). If you checked for variations in the levels of tyrosine phosphorylated STAT1/3, you may have missed the differences in the serine phosphorylation. My suggestion would be to run EMSA's or follow the experimental procedures in the Cantrell and Larner papers. Third: analysis of the promoter sequences may not be enough. Have you checked also the enhancers? A detailed analysis of the promoter and enhancer sequences of the two genes may give you additional clues. Follow this link: http://transfac.gbf.de/programs.html You will be able to use the MatInspector software to determine which transcription factors are likely to bind to a given DNA sequence. Clearly this provides only an indication, but it may be a good start.